Known examples of biodegradable and bioabsorbable polymers include polylactic acid, polyglycolic acid, polycaprolactone, trimethylene carbonate, polydioxane, copolymers thereof, and the like. They are degradable and absorbable in vivo, and are thus used in medical implant applications such as sutures, bone-joining materials, etc.
Since a heavy metal-based catalyst such as tin octylate is widely used for the synthesis of such a polymer compound, the metal catalyst remains in the synthesized polymer compound. When the polymer compound is used as a material for a medical implant application, the metal catalyst is exposed to the body with the degradation of the polymer. The metal catalyst, which varies according to species, may have harmful effects on the human body such as immunotoxicity, genetic toxicity, neurotoxicity, etc. when present at a certain concentration or more. Therefore, when the polymer is used in a medical implant application, the metal catalyst residual content must be reduced as much as possible.
On the other hand, polymers for implant applications require features of a certain level or more of molecular weight, strength, etc. In order to obtain such polymers, a metal catalyst of a certain amount or more must be added during the polymerization process; it is thus required to remove the metal catalyst remaining in the polymer after the polymerization reaction. However, removal of the metal catalyst is not easy, and is often accompanied by industrial difficulties.
For example, in a method described in Patent Document 1, a polymer compound is first dissolved in an organic solvent, and a metal catalyst is then removed by reprecipitation. This method, however, requires a large amount of solvent, and causes a drastic drop in molecular weight due to the polymer dissolution. Therefore, this is not appropriate for producing materials (e.g., medical devices) that require strength of a certain level or more. Furthermore, since the polymer tends to contain many air bubbles when reprecipitated, the molded product of the polymer is also likely to contain bubbles. Thus, it is not suitable for industrial manufacture.
Patent Document 2 discloses a method for producing copolymers of lactide and ε-caprolactone; however, it does not disclose the final metal catalyst content. The publication discloses that the catalyst is used in an amount of 10−7 to 10−3 mol/mol relative to the monomers; however, the Examples merely disclose that a catalyst is added in an amount of 10−5 mol (metal content: 22 ppm) per mol of monomer. The further reduction of the metal catalyst content is not specifically disclosed.
Patent Document 3 discloses a method for obtaining a biodegradable and bioabsorbable polymer having a high molecular weight by adding 1 to 20 ppm of a metal catalyst and 0.01 to 0.5 wt % of higher alcohol to lactide and caprolactone, and by conducting polymerization under reduced pressure for 10 to 40 days. However, since the end of the polymer obtained by this method is modified with a higher alcohol, it is considered that the polymer has different properties (e.g., absorbability, safety) than previously used bioabsorbable polymers, and thus various examinations are required. Furthermore, since the metal catalyst content used is too small, a long polymerization period is required. It is therefore not industrially preferable.    Patent Document 1:    Japanese Unexamined Patent Publication No. S60-501217, see Example I, etc.    Patent Document 2:    Japanese Unexamined Patent Publication No. H6-501045    Patent Document 3:Japanese Unexamined Patent Publication No. 2000-191753